Chronic pain is devastating both to individuals and society. In an aging population, surgery is an increasing cause of chronic pain, with rates of persistent post-operative pain ranging from 10-65%. In particular, Persistent Post-Mastectomy Pain (PPMP) occurs in roughly one third of women who have had mastectomy. The occurrence of PPMP does not seem to be strongly determined by the type of surgery, chemotherapy, and radiation treatment, suggesting that individual person-specific factors may play a more important role. In fact, recent studies by the candidate indicate that individual differences in pain sensitiity (psychophysics) are more closely associated with PPMP than surgical/medical variables. Specifically, sensory testing revealed that women who developed PPMP had lower pressure pain thresholds and greater temporal summation of pain stimuli than women who did not develop this chronic pain condition. Moreover, psychosocial factors such as anxiety, depression, catastrophizing, and somatization were more prominent in women with PPMP. These preliminary, retrospective studies suggest that individual psychophysical and psychosocial characteristics could be important risk factors for PPMP. Accordingly, the first Aim of this study is to comprehensively and prospectively study women having mastectomy surgery, to determine the relationship between pre-operative psychophysical and psychosocial factors and the development of PPMP. The second Aim is to develop a prediction model for PPMP using the data collected in Aim 1, thus allowing a preoperative calculation of a PPMP risk score for any patient facing mastectomy. This will then be validated in a separate group of patients (study 2). Study will be this risk score will be used to enrich an interventional trial with a greater proporton of women at high risk of PPMP, with Aim 3 to investigate whether this enrichment allows more efficient and sensitive determination of a preventative drug's effect than in an unscreened group. These studies will lay the groundwork to efficiently test novel pharmaceutics only in the high risk patients who need them. The candidate in this application, Dr. Kristin Schreiber is a PhD-trained Neuroscientist and Anesthesiologist at a leading academic, high-volume breast cancer center. The proposed studies would inform healthcare providers about the underlying mechanisms contributing to chronic pain after surgery, thus allowing more targeted, preventive treatment in patients who are high risk for persisting post-operative pain. Her career development mentors are experts in surgical, medical, psychological, and preoperative assessment, preclinical modeling, and biostatistics. The candidate's strong scientific background, taken together with the proposed formal training in advanced statistics and diverse mentorship, in a center that has a strong tradition and infrastructure for clinical trials, will enure the successful achievement of her scientific and career objectives to prevent PPMP and lay the groundwork for prevention of other persistent post-surgical pain syndromes.